Abstract Body: Case Presentation:
Carvedilol is widely used in cirrhosis to reduce portal hypertension and prevent variceal bleeding. While generally considered safe, carvedilol’s pharmacokinetics can be altered in hepatic impairment with increased bioavailability and prolonged half-life. Cirrhosis may also cause hemodynamic sensitivity. These physiologic and pharmacokinetic changes in cirrhosis are underrecognized, and administration of carvedilol can lead to serious adverse effects, even at standard doses. In this case a 42-year-old female with a history of cirrhosis from hepatitis C and ESRD presented to the hospital with dyspnea. Imaging showed pneumonia. Labs showed ALT 9 units/L, AST 11 units/L, and a Child-Pugh score of 6 (bilirubin 0.4 mg/dL, albumin 3.1 g/dL, INR 1.5, ammonia <15 umol/L). All other labs were unremarkable. Carvedilol had been discontinued many months prior. However, it was erroneously listed as active on medication reconciliation, and 12.5 mg was administered. BP and HR at administration were 117/88 and 70 bpm, respectively. One hours later, BP dropped to 79/48 mmHg and HR to 37 bpm. associated with symptoms of lethargy and dizziness. Echocardiogram showed ejection fraction 65–70% and normal left ventricular size.
Management and Outcome:
Atropine and glucagon 2 mg were administered without improvement; thus, epinephrine and norepinephrine were started, titrated, infused for two hours with minimal clinical change. High-dose insulin was then added running at 0.5 units/kg/hr due to insulin naivety. Patient experienced prompt improvement within one hour of starting insulin therapy. Bradycardia persisted for 7 hours before resolving, where she was eventaully treated for pneumonia and discharged without complications
Discussion:
This case highlights the underappreciated risk of carvedilol toxicity in cirrhosis. Carvedilol is metabolized by the liver, and cirrhosis can increase systemic exposure by 2.5–4 times due to reduced first-pass metabolism, impaired clearance, and hypoalbuminemia. Though not renally cleared, missed dialysis may have worsened the clinical picture through fluid or metabolic effects. This patient’s response required intensive interventions and close monitoring for several hours. Carvedilol’s altered pharmacokinetics in cirrhosis are often overlooked. Even a standard dose can cause life-threatening bradycardia and hypotension. Careful review of medication history and individualized risk assessment are critical in this population.